Our ongoing and central goal is to produce experimental evidence, complete annotation, and a representative cDNA clone for every protein-coding gene in the Drosophila melanogaster genome. Further, we plan to continue our studies to characterize and annotate the extent of splice variation used to generate protein isoforms in D, melanogaster. At the Berkeley Drosophila Genome Project (BDGP) we have generated and sequenced a large set of expressed sequence tags (ESTs) that have given rise to the Drosophila Gene Collection (DGC). We propose to complete this unigene DGC. We plan to use a variety of methods including inverse PCR and RT-PCR to identify and isolate clones for rarely expressed genes. As a public resource, completeness is essential for functional studies of genes and their corresponding proteins. cDNA clones provide the best experimental evidence of transcription, transcript processing and gene structure. They are also a critical resource for proteomics directed at studying medically relevant classes of genes, kinases, transcription factors and receptors. Partial sets of clones are not adequate for comprehensive functional genomic studies. These studies will provide information and tools that will elucidate the complete transcriptome in Drosophila melanogaster, a prerequisite for understanding normal growth and differentiation and that will aid in understanding these processes in other organisms including humans. Drosophila models have been developed for Alzheimer and other neurodegenerative diseases and cancer. In addition, genes first identified to play a role in Drosophila development are often components of conserved regulatory networks that play important roles during animal development and have been found, in humans, to contribute to the development of a variety of human cancers. [unreadable] [unreadable] [unreadable]